Type 2 Diabetes
Conditions
Brief summary
The main purpose of this study is to evaluate the efficacy and safety of LY3437943 in participants with type 2 diabetes (T2D) who failed to achieve adequate glycemic control on diet and exercise alone or on a stable dose of metformin. This study will last about 43 weeks.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have Type 2 Diabetes (T2D) * Have an HbA1c value at screening of ≥7.0% and ≤10.5% and treated with diet and exercise alone or with a stable dose of metformin (either immediate release or extended release, 1000 milligram (mg)/day and not more than the locally approved dose) for at least 3 months prior to screening.
Exclusion criteria
* Have type 1 diabetes mellitus (T1DM) * Have ketoacidosis * Have retinopathy, maculopathy * Have history of pancreatitis * Have obesity induced by other endocrine disorders * Have uncontrolled hypertension * Have acute or chronic hepatitis * Have chronic kidney disease * Have an autoimmune abnormality for example, lupus or rheumatoid arthritis * Have an active or untreated malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) | Baseline, 24 Weeks | Change in HbA1c (%) from baseline in LY3437943 relative to placebo. HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reaching HbA1c <7.0% | Week 24 | Percentage of participants reaching HbA1c \<7.0% in LY3437943 relative to placebo and dulaglutide. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum \[\<30 kg/m2, ≥30 kg/m2\] as fixed effects, and baseline HbA1c value as a covariate. |
| Percentage of Participant Reaching HbA1c <7.0% | Week 36 | Percentage of participants reaching HbA1c \<7.0% in LY3437943 relative to placebo and dulaglutide. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum \[\<30 kg/m2, ≥30 kg/m2\] as fixed effects, and baseline HbA1c value as a covariate. |
| Change From Baseline in HbA1c | Baseline, 24 Weeks | Change in HbA1c (%) from baseline in LY3437943 relative to dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time. |
| Change From Baseline in Body Weight | Baseline, 24 Weeks | Change in body weight from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time. |
| Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | Predose: Week 0, 1, 4, 12, 24, 30; Postdose: Week 2, 8, 16, 20, 36 | The average steady-state plasma concentration of LY3437943 was evaluated using sparse sampling methodology/Population PK (PopPK) modeling. |
| Change From Baseline in Fasting Blood Glucose (FBG) | Baseline, 24 Weeks | Change in FBG from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Four maintenance doses of LY3437943 were evaluated: 0.5 mg, 4 mg, 8 mg, and 12 mg. Dose escalation occurred in certain cohorts up to Week 12 during the 36-week treatment period. For maintenance doses equal to or greater than 4 mg, the initial dose will be 2 mg or 4 mg followed by additional escalation steps as appropriate.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered as SC injection QW. | 45 |
| 1.5 mg Dulaglutide Participants received 1.5 mg dulaglutide administered as SC single-dose pen injection QW. | 46 |
| 0.5 mg LY3437943 Participants received 0.5 mg LY3437943 administered as SC injection QW. | 47 |
| 4 mg LY3437943 (2 mg) Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 administered as SC injection QW. | 23 |
| 4 mg LY3437943 (4 mg) Participants received 4 mg LY3437943 administered as SC injection QW. | 24 |
| 8 mg LY3437943 (2 mg) Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 and then 8 mg LY3437943 administered as SC injection QW. | 26 |
| 8 mg LY3437943 (4 mg) Participants received 4 mg LY3437943 starting dose followed by 8 mg LY3437943 administered as SC injection QW. | 24 |
| 12 mg LY3437943 (2 mg) Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943, then 8 mg LY3437943, then 12 mg LY3437943 administered as SC injection QW. | 46 |
| Total | 281 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Eligibility Criteria Not Met | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Inadvertent Enrollment | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 4 | 3 | 2 | 0 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 2 | 2 | 1 | 2 | 0 | 2 | 5 |
Baseline characteristics
| Characteristic | Placebo | 1.5 mg Dulaglutide | 0.5 mg LY3437943 | 4 mg LY3437943 (2 mg) | 4 mg LY3437943 (4 mg) | 8 mg LY3437943 (2 mg) | 8 mg LY3437943 (4 mg) | 12 mg LY3437943 (2 mg) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.56 years STANDARD_DEVIATION 10.83 | 54.94 years STANDARD_DEVIATION 10.45 | 57.21 years STANDARD_DEVIATION 9.69 | 57.70 years STANDARD_DEVIATION 8.14 | 57.58 years STANDARD_DEVIATION 10 | 57.00 years STANDARD_DEVIATION 7.37 | 53.83 years STANDARD_DEVIATION 9.03 | 54.37 years STANDARD_DEVIATION 9.72 | 56.19 years STANDARD_DEVIATION 9.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 20 Participants | 27 Participants | 9 Participants | 13 Participants | 12 Participants | 9 Participants | 20 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 26 Participants | 20 Participants | 14 Participants | 10 Participants | 14 Participants | 15 Participants | 26 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Percentage of Hemoglobin A1c (HbA1c) at Baseline | 8.39 Percentage of HbA1c STANDARD_DEVIATION 1.139 | 8.22 Percentage of HbA1c STANDARD_DEVIATION 0.919 | 8.35 Percentage of HbA1c STANDARD_DEVIATION 1.172 | 8.07 Percentage of HbA1c STANDARD_DEVIATION 0.87 | 8.20 Percentage of HbA1c STANDARD_DEVIATION 1.207 | 8.34 Percentage of HbA1c STANDARD_DEVIATION 1.12 | 8.20 Percentage of HbA1c STANDARD_DEVIATION 1.261 | 8.28 Percentage of HbA1c STANDARD_DEVIATION 1.066 | 8.27 Percentage of HbA1c STANDARD_DEVIATION 1.086 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 6 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 36 Participants | 36 Participants | 40 Participants | 20 Participants | 22 Participants | 23 Participants | 20 Participants | 38 Participants | 235 Participants |
| Region of Enrollment United States | 45 participants | 46 participants | 47 participants | 23 participants | 24 participants | 26 participants | 24 participants | 46 participants | 281 participants |
| Sex: Female, Male Female | 23 Participants | 33 Participants | 23 Participants | 8 Participants | 12 Participants | 16 Participants | 15 Participants | 26 Participants | 156 Participants |
| Sex: Female, Male Male | 22 Participants | 13 Participants | 24 Participants | 15 Participants | 12 Participants | 10 Participants | 9 Participants | 20 Participants | 125 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 46 | 0 / 47 | 0 / 23 | 0 / 24 | 0 / 26 | 0 / 24 | 0 / 46 |
| other Total, other adverse events | 15 / 45 | 24 / 46 | 15 / 47 | 9 / 23 | 17 / 24 | 16 / 26 | 15 / 24 | 25 / 46 |
| serious Total, serious adverse events | 3 / 45 | 1 / 46 | 3 / 47 | 1 / 23 | 2 / 24 | 2 / 26 | 1 / 24 | 2 / 46 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c)
Change in HbA1c (%) from baseline in LY3437943 relative to placebo. HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time.
Time frame: Baseline, 24 Weeks
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) | -0.05 percentage of HbA1c | Standard Error 0.21 |
| 1.5 mg Dulaglutide | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.41 percentage of HbA1c | Standard Error 0.12 |
| 0.5 mg LY3437943 | Change From Baseline in Hemoglobin A1c (HbA1c) | -0.43 percentage of HbA1c | Standard Error 0.2 |
| 4 mg LY3437943 (2 mg) | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.39 percentage of HbA1c | Standard Error 0.14 |
| 4 mg LY3437943 (4 mg) | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.30 percentage of HbA1c | Standard Error 0.22 |
| 8 mg LY3437943 (2 mg) | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.99 percentage of HbA1c | Standard Error 0.15 |
| 8 mg LY3437943 (4 mg) | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.88 percentage of HbA1c | Standard Error 0.21 |
| 12 mg LY3437943 (2 mg) | Change From Baseline in Hemoglobin A1c (HbA1c) | -2.01 percentage of HbA1c | Standard Error 0.11 |
p-value: 0.18895% CI: [-0.94, 0.18]Mixed Models Analysis
p-value: <0.00195% CI: [-1.84, -0.85]Mixed Models Analysis
p-value: <0.00195% CI: [-1.85, -0.65]Mixed Models Analysis
p-value: <0.00195% CI: [-2.44, -1.43]Mixed Models Analysis
p-value: <0.00195% CI: [-2.42, -1.24]Mixed Models Analysis
p-value: <0.00195% CI: [-2.43, -1.5]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
Change in body weight from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Baseline HbA1c Group (\<=8.5%, \>8.5%)\*Time + Baseline BMI Group (\<30kg/m2, \>=30kg/m2)\*Time + Baseline\*Time.
Time frame: Baseline, 36 Weeks
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight | -3.28 kilograms (kg) | Standard Error 0.92 |
| 1.5 mg Dulaglutide | Change From Baseline in Body Weight | -1.97 kilograms (kg) | Standard Error 0.87 |
| 0.5 mg LY3437943 | Change From Baseline in Body Weight | -3.31 kilograms (kg) | Standard Error 0.62 |
| 4 mg LY3437943 (2 mg) | Change From Baseline in Body Weight | -7.28 kilograms (kg) | Standard Error 1.39 |
| 4 mg LY3437943 (4 mg) | Change From Baseline in Body Weight | -10.37 kilograms (kg) | Standard Error 1.49 |
| 8 mg LY3437943 (2 mg) | Change From Baseline in Body Weight | -16.48 kilograms (kg) | Standard Error 1.55 |
| 8 mg LY3437943 (4 mg) | Change From Baseline in Body Weight | -16.12 kilograms (kg) | Standard Error 1.63 |
| 12 mg LY3437943 (2 mg) | Change From Baseline in Body Weight | -17.18 kilograms (kg) | Standard Error 1.32 |
p-value: 0.97995% CI: [-2.18, 2.12]Mixed Models Analysis
p-value: 0.01895% CI: [-7.32, -0.68]Mixed Models Analysis
p-value: <0.00195% CI: [-10.46, -3.71]Mixed Models Analysis
p-value: <0.00195% CI: [-16.74, -9.66]Mixed Models Analysis
p-value: <0.00195% CI: [-16.5, -9.18]Mixed Models Analysis
p-value: <0.00195% CI: [-17.1, -10.71]Mixed Models Analysis
p-value: 0.21395% CI: [-3.45, 0.77]Mixed Models Analysis
p-value: 0.00295% CI: [-8.66, -1.97]Mixed Models Analysis
p-value: <0.00195% CI: [-11.76, -5.04]Mixed Models Analysis
p-value: <0.00195% CI: [-18, -11.01]Mixed Models Analysis
p-value: <0.00195% CI: [-17.77, -10.54]Mixed Models Analysis
p-value: <0.00195% CI: [-18.36, -12.07]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
Change in body weight from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time.
Time frame: Baseline, 24 Weeks
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight | -1.86 kilograms (kg) | Standard Error 0.66 |
| 1.5 mg Dulaglutide | Change From Baseline in Body Weight | -1.16 kilograms (kg) | Standard Error 0.63 |
| 0.5 mg LY3437943 | Change From Baseline in Body Weight | -2.35 kilograms (kg) | Standard Error 0.48 |
| 4 mg LY3437943 (2 mg) | Change From Baseline in Body Weight | -6.27 kilograms (kg) | Standard Error 0.94 |
| 4 mg LY3437943 (4 mg) | Change From Baseline in Body Weight | -8.64 kilograms (kg) | Standard Error 1.23 |
| 8 mg LY3437943 (2 mg) | Change From Baseline in Body Weight | -11.99 kilograms (kg) | Standard Error 0.84 |
| 8 mg LY3437943 (4 mg) | Change From Baseline in Body Weight | -13.91 kilograms (kg) | Standard Error 1.38 |
| 12 mg LY3437943 (2 mg) | Change From Baseline in Body Weight | -12.84 kilograms (kg) | Standard Error 0.93 |
p-value: 0.5495% CI: [-2.07, 1.08]Mixed Models Analysis
p-value: <0.00195% CI: [-6.69, -2.13]Mixed Models Analysis
p-value: <0.00195% CI: [-9.47, -4.09]Mixed Models Analysis
p-value: <0.00195% CI: [-12.24, -8.03]Mixed Models Analysis
p-value: <0.00195% CI: [-15.06, -9.06]Mixed Models Analysis
p-value: <0.00195% CI: [-13.24, -8.73]Mixed Models Analysis
p-value: 0.13595% CI: [-2.75, 0.37]Mixed Models Analysis
p-value: <0.00195% CI: [-7.36, -2.86]Mixed Models Analysis
p-value: <0.00195% CI: [-10.19, -4.77]Mixed Models Analysis
p-value: <0.00195% CI: [-12.89, -8.77]Mixed Models Analysis
p-value: <0.00195% CI: [-15.74, -9.77]Mixed Models Analysis
p-value: <0.00195% CI: [-13.9, -9.47]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Blood Glucose (FBG)
Change in FBG from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time.
Time frame: Baseline, 24 Weeks
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Blood Glucose (FBG) | -10.59 milligrams/deciliter (mg/dL) | Standard Error 5.98 |
| 1.5 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) | -46.26 milligrams/deciliter (mg/dL) | Standard Error 4.35 |
| 0.5 mg LY3437943 | Change From Baseline in Fasting Blood Glucose (FBG) | -12.71 milligrams/deciliter (mg/dL) | Standard Error 6.95 |
| 4 mg LY3437943 (2 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -30.19 milligrams/deciliter (mg/dL) | Standard Error 12.65 |
| 4 mg LY3437943 (4 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -43.89 milligrams/deciliter (mg/dL) | Standard Error 8.42 |
| 8 mg LY3437943 (2 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -66.09 milligrams/deciliter (mg/dL) | Standard Error 3.7 |
| 8 mg LY3437943 (4 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -39.80 milligrams/deciliter (mg/dL) | Standard Error 10.79 |
| 12 mg LY3437943 (2 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -65.20 milligrams/deciliter (mg/dL) | Standard Error 4.38 |
p-value: 0.82395% CI: [-20.73, 16.48]Mixed Models Analysis
p-value: 0.16595% CI: [-47.29, 8.1]Mixed Models Analysis
p-value: 0.00195% CI: [-53.56, -13.04]Mixed Models Analysis
p-value: <0.00195% CI: [-69.77, -41.22]Mixed Models Analysis
p-value: 0.01595% CI: [-52.84, -5.59]Mixed Models Analysis
p-value: <0.00195% CI: [-69.63, -39.59]Mixed Models Analysis
p-value: <0.00195% CI: [18.26, 48.82]Mixed Models Analysis
p-value: 0.23195% CI: [-10.25, 42.39]Mixed Models Analysis
p-value: 0.80495% CI: [-16.28, 21.01]Mixed Models Analysis
p-value: <0.00195% CI: [-31.01, -8.65]Mixed Models Analysis
p-value: 0.58695% CI: [-16.75, 29.65]Mixed Models Analysis
p-value: 0.00295% CI: [-30.93, -6.96]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Blood Glucose (FBG)
Change in FBG from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Baseline HbA1c Group (\<=8.5%, \>8.5%)\*Time + Baseline BMI Group (\<30kg/m2, \>=30kg/m2)\*Time + Baseline\*Time.
Time frame: Baseline, 36 Weeks
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Blood Glucose (FBG) | -17.26 mg/dL | Standard Error 10.87 |
| 1.5 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) | -27.53 mg/dL | Standard Error 9.07 |
| 0.5 mg LY3437943 | Change From Baseline in Fasting Blood Glucose (FBG) | -17.51 mg/dL | Standard Error 5.59 |
| 4 mg LY3437943 (2 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -21.46 mg/dL | Standard Error 12.54 |
| 4 mg LY3437943 (4 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -38.72 mg/dL | Standard Error 10.81 |
| 8 mg LY3437943 (2 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -69.10 mg/dL | Standard Error 4.68 |
| 8 mg LY3437943 (4 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -41.20 mg/dL | Standard Error 14.43 |
| 12 mg LY3437943 (2 mg) | Change From Baseline in Fasting Blood Glucose (FBG) | -67.84 mg/dL | Standard Error 4.79 |
p-value: 0.98495% CI: [-24.57, 24.07]Mixed Models Analysis
p-value: 0.80495% CI: [-37.44, 29.03]Mixed Models Analysis
p-value: 0.16795% CI: [-51.91, 8.98]Mixed Models Analysis
p-value: <0.00195% CI: [-76.09, -27.59]Mixed Models Analysis
p-value: 0.16895% CI: [-57.94, 10.06]Mixed Models Analysis
p-value: <0.00195% CI: [-74.94, -26.22]Mixed Models Analysis
p-value: 0.36295% CI: [-11.55, 31.6]Mixed Models Analysis
p-value: 0.69695% CI: [-24.34, 36.48]Mixed Models Analysis
p-value: 0.43695% CI: [-39.38, 16.99]Mixed Models Analysis
p-value: <0.00195% CI: [-62.89, -20.25]Mixed Models Analysis
p-value: 0.41895% CI: [-46.75, 19.42]Mixed Models Analysis
p-value: <0.00195% CI: [-60.77, -19.85]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c
Change in HbA1c (%) from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Baseline HbA1c Group (\<=8.5%, \>8.5%)\*Time + Baseline Body Mass Index (BMI) Group (\<30 kilograms/square meter (kg/m2), \>=30 kg/m2)\*Time + Baseline\*Time.
Time frame: Baseline, 36 Weeks
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c | -0.30 percentage of HbA1c | Standard Error 0.24 |
| 1.5 mg Dulaglutide | Change From Baseline in HbA1c | -1.36 percentage of HbA1c | Standard Error 0.13 |
| 0.5 mg LY3437943 | Change From Baseline in HbA1c | -0.54 percentage of HbA1c | Standard Error 0.2 |
| 4 mg LY3437943 (2 mg) | Change From Baseline in HbA1c | -1.30 percentage of HbA1c | Standard Error 0.2 |
| 4 mg LY3437943 (4 mg) | Change From Baseline in HbA1c | -1.50 percentage of HbA1c | Standard Error 0.19 |
| 8 mg LY3437943 (2 mg) | Change From Baseline in HbA1c | -2.13 percentage of HbA1c | Standard Error 0.17 |
| 8 mg LY3437943 (4 mg) | Change From Baseline in HbA1c | -1.93 percentage of HbA1c | Standard Error 0.22 |
| 12 mg LY3437943 (2 mg) | Change From Baseline in HbA1c | -2.16 percentage of HbA1c | Standard Error 0.13 |
p-value: 0.44895% CI: [-0.85, 0.38]Mixed Models Analysis
p-value: 0.00195% CI: [-1.6, -0.38]Mixed Models Analysis
p-value: <0.00195% CI: [-1.8, -0.59]Mixed Models Analysis
p-value: <0.00195% CI: [-2.41, -1.24]Mixed Models Analysis
p-value: <0.00195% CI: [-2.27, -0.99]Mixed Models Analysis
p-value: <0.00195% CI: [-2.39, -1.31]Mixed Models Analysis
p-value: <0.00195% CI: [0.35, 1.29]Mixed Models Analysis
p-value: 0.79695% CI: [-0.41, 0.53]Mixed Models Analysis
p-value: 0.54895% CI: [-0.61, 0.32]Mixed Models Analysis
p-value: <0.00195% CI: [-1.19, -0.36]Mixed Models Analysis
p-value: 0.02595% CI: [-1.08, -0.07]Mixed Models Analysis
p-value: <0.00195% CI: [-1.16, -0.44]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c
Change in HbA1c (%) from baseline in LY3437943 relative to dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment\*Time + Strata\*Time + Baseline\*Time.
Time frame: Baseline, 24 Weeks
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c | -0.05 percentage of HbA1c | Standard Error 0.21 |
| 1.5 mg Dulaglutide | Change From Baseline in HbA1c | -1.41 percentage of HbA1c | Standard Error 0.12 |
| 0.5 mg LY3437943 | Change From Baseline in HbA1c | -0.43 percentage of HbA1c | Standard Error 0.2 |
| 4 mg LY3437943 (2 mg) | Change From Baseline in HbA1c | -1.39 percentage of HbA1c | Standard Error 0.14 |
| 4 mg LY3437943 (4 mg) | Change From Baseline in HbA1c | -1.30 percentage of HbA1c | Standard Error 0.22 |
| 8 mg LY3437943 (2 mg) | Change From Baseline in HbA1c | -1.99 percentage of HbA1c | Standard Error 0.15 |
| 8 mg LY3437943 (4 mg) | Change From Baseline in HbA1c | -1.88 percentage of HbA1c | Standard Error 0.21 |
| 12 mg LY3437943 (2 mg) | Change From Baseline in HbA1c | -2.01 percentage of HbA1c | Standard Error 0.11 |
p-value: <0.00195% CI: [0.52, 1.43]Mixed Models Analysis
p-value: 0.93595% CI: [-0.34, 0.37]Mixed Models Analysis
p-value: 0.66895% CI: [-0.39, 0.6]Mixed Models Analysis
p-value: 0.00295% CI: [-0.95, -0.21]Mixed Models Analysis
p-value: 0.05695% CI: [-0.95, 0.01]Mixed Models Analysis
p-value: <0.00195% CI: [-0.93, -0.29]Mixed Models Analysis
Secondary
Percentage of Participant Reaching HbA1c <7.0%
Percentage of participants reaching HbA1c \<7.0% in LY3437943 relative to placebo and dulaglutide. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum \[\<30 kg/m2, ≥30 kg/m2\] as fixed effects, and baseline HbA1c value as a covariate.
Time frame: Week 36
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participant Reaching HbA1c <7.0% | 22 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participant Reaching HbA1c <7.0% | 60 percentage of participants |
| 0.5 mg LY3437943 | Percentage of Participant Reaching HbA1c <7.0% | 37 percentage of participants |
| 4 mg LY3437943 (2 mg) | Percentage of Participant Reaching HbA1c <7.0% | 61 percentage of participants |
| 4 mg LY3437943 (4 mg) | Percentage of Participant Reaching HbA1c <7.0% | 59 percentage of participants |
| 8 mg LY3437943 (2 mg) | Percentage of Participant Reaching HbA1c <7.0% | 82 percentage of participants |
| 8 mg LY3437943 (4 mg) | Percentage of Participant Reaching HbA1c <7.0% | 78 percentage of participants |
| 12 mg LY3437943 (2 mg) | Percentage of Participant Reaching HbA1c <7.0% | 80 percentage of participants |
p-value: 0.16995% CI: [-0.06, 0.35]Regression, Logistic
p-value: 0.00195% CI: [0.15, 0.63]Regression, Logistic
p-value: 0.00295% CI: [0.14, 0.6]Regression, Logistic
p-value: <0.00195% CI: [0.39, 0.79]Regression, Logistic
p-value: <0.00195% CI: [0.34, 0.78]Regression, Logistic
p-value: <0.00195% CI: [0.38, 0.76]Regression, Logistic
p-value: 0.02995% CI: [-0.44, -0.02]Regression, Logistic
p-value: 0.89895% CI: [-0.22, 0.25]Regression, Logistic
p-value: 0.96895% CI: [-0.24, 0.23]Regression, Logistic
p-value: 0.03395% CI: [0.02, 0.42]Regression, Logistic
p-value: 0.09995% CI: [-0.04, 0.41]Regression, Logistic
p-value: 0.04495% CI: [0.01, 0.39]Regression, Logistic
Secondary
Percentage of Participants Reaching HbA1c <7.0%
Percentage of participants reaching HbA1c \<7.0% in LY3437943 relative to placebo and dulaglutide. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum \[\<30 kg/m2, ≥30 kg/m2\] as fixed effects, and baseline HbA1c value as a covariate.
Time frame: Week 24
Population: All randomized participants with baseline and post-baseline value at the specified time point excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Reaching HbA1c <7.0% | 18 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants Reaching HbA1c <7.0% | 52 percentage of participants |
| 0.5 mg LY3437943 | Percentage of Participants Reaching HbA1c <7.0% | 32 percentage of participants |
| 4 mg LY3437943 (2 mg) | Percentage of Participants Reaching HbA1c <7.0% | 53 percentage of participants |
| 4 mg LY3437943 (4 mg) | Percentage of Participants Reaching HbA1c <7.0% | 66 percentage of participants |
| 8 mg LY3437943 (2 mg) | Percentage of Participants Reaching HbA1c <7.0% | 88 percentage of participants |
| 8 mg LY3437943 (4 mg) | Percentage of Participants Reaching HbA1c <7.0% | 78 percentage of participants |
| 12 mg LY3437943 (2 mg) | Percentage of Participants Reaching HbA1c <7.0% | 86 percentage of participants |
p-value: 0.12195% CI: [-0.04, 0.32]Regression, Logistic
p-value: 0.00295% CI: [0.13, 0.59]Regression, Logistic
p-value: <0.00195% CI: [0.28, 0.68]Regression, Logistic
p-value: <0.00195% CI: [0.53, 0.87]Regression, Logistic
p-value: <0.00195% CI: [0.39, 0.82]Regression, Logistic
p-value: <0.00195% CI: [0.51, 0.85]Regression, Logistic
p-value: 0.0395% CI: [-0.39, -0.02]Regression, Logistic
p-value: 0.93895% CI: [-0.22, 0.24]Regression, Logistic
p-value: 0.20995% CI: [-0.07, 0.33]Regression, Logistic
p-value: <0.00195% CI: [0.18, 0.53]Regression, Logistic
p-value: 0.02495% CI: [0.03, 0.48]Regression, Logistic
p-value: <0.00195% CI: [0.16, 0.51]Regression, Logistic
Secondary
Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943
The average steady-state plasma concentration of LY3437943 was evaluated using sparse sampling methodology/Population PK (PopPK) modeling.
Time frame: Predose: Week 0, 1, 4, 12, 24, 30; Postdose: Week 2, 8, 16, 20, 36
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | 62.8 nanograms/milliliter (ng/mL) |
| 1.5 mg Dulaglutide | Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | 466 nanograms/milliliter (ng/mL) |
| 0.5 mg LY3437943 | Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | 551 nanograms/milliliter (ng/mL) |
| 4 mg LY3437943 (2 mg) | Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | 1100 nanograms/milliliter (ng/mL) |
| 4 mg LY3437943 (4 mg) | Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | 1140 nanograms/milliliter (ng/mL) |
| 8 mg LY3437943 (2 mg) | Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | 1620 nanograms/milliliter (ng/mL) |